The endothelium modulates the vascular smooth muscle response to endogenous constrictor substances by either inactivating them metabolically or by releasing its own vasoactive agent(s). Normally, there is a delicate balance between dilators and constrictors. This balance is lost in some disease states. Little is known about the effect of pregnancy upon endothelial function. Pregnancy is associated with a reduction in sensitivity to many endogenous constrictors, a decrease in vascular resistance, and a redistribution of an increased cardiac output. The stimuli directly responsible for these alterations are unclear and it is unknown if they are linked. Pregnancy is associated with increased endothelium derived relaxing factor (EDRF) in the uterine artery. The decreased uterine artery contractile responses to norepinephrine during pregnancy are secondary to EDRF. We hypothesize that the endothelium or reproductively important vascular beds are hormonally altered during pregnancy resulting in enhanced tonic and stimulated release of endothelial dilators and decreased release of constrictors. We further hypothesize that these changes are directly responsible for the redistribution of maternal cardiac output to organs crucial for a successful pregnancy and the reduction in vascular sensitivity to constrictor agents. Specific Aim 1: To determine the time course of NO-EDRF release and endothelial mechanisms which mediate the increase in EDRF during pregnancy. Specific Aim 2: To determine whether the tonic or stimulated release of NO-EDRF is estrogen dependent. Specific Aim 3: To determine whether the increased ACh-EDRF activity during pregnancy or after estrogen pretreatment parallels a change in muscarinic receptor status. Specific Aim 4: To determine whether the effect of pregnancy upon endothelium-derived vasoactive factors differs among arteries and veins from "reproductive" and "nonreproductive" organs.